Despite excellent rates of local control, uveal melanoma, the most common intraocular malignancy, remains lethal in a large proportion of patients due to the lack of treatments for metastatic disease. This application proposes a systematic search for somatic mutations in a large panel of cancer genes in uveal melanoma specimens using a high- throughput, mass spectrometry-based genotyping technology. Using this technology, we will screen for known mutations in over 100 oncogenes and tumor suppressor genes in order to identify specific mutations prevalent in uveal melanoma, establish correlations between particular mutations and clinical outcome, and begin to confirm the functional significance of these mutations in vitro. These studies will provide an important step towards development of rationally-designed, targeted adjuvant chemotherapy necessary for improved survival of patients with the most common intraocular malignancy. PUBLIC HEALTH RELEVANCE: Uveal melanoma is the most common intraocular cancer, and currently, there is no effective treatment for this cancer once it spreads outside the eye. This project will search for over 100 known cancer-causing mutations in this tumor type in hopes of finding targets for new drugs that will improve the survival of patients with this malignancy.